Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)

Mavurapu Satyanarayana; Wei Feng; Liang Cheng; Angela A. Liu; Yuan Chin Tsai; Leroy F. Liu; Edmond J. LaVoie

doi:10.1016/j.bmc.2008.06.046

Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)

Mavurapu Satyanarayana, Wei Feng, Liang Cheng, Angela A. Liu, Yuan Chin Tsai, Leroy F. Liu, Edmond J. LaVoie

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.

Original language	English
Pages (from-to)	7824-7831
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	16
DOIs	https://doi.org/10.1016/j.bmc.2008.06.046
Publication status	Published - Aug 15 2008
Externally published	Yes

Keywords

Antitumor
Athymic mice
Cinnolines
Cytotoxicity
Human tumor xenografts
Isoquino[4,3-c]cinnolin-12-ones
Multidrug resistance
Topoisomerase

ASJC Scopus subject areas

Drug Discovery
Molecular Medicine
Molecular Biology
Biochemistry
Clinical Biochemistry
Pharmaceutical Science
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2008.06.046

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Satyanarayana, M., Feng, W., Cheng, L., Liu, A. A., Tsai, Y. C., Liu, L. F., & LaVoie, E. J. (2008). Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31). Bioorganic and Medicinal Chemistry, 16(16), 7824-7831. https://doi.org/10.1016/j.bmc.2008.06.046

Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31). / Satyanarayana, Mavurapu; Feng, Wei; Cheng, Liang et al.
In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 16, 15.08.2008, p. 7824-7831.

Research output: Contribution to journal › Article › peer-review

Satyanarayana, M, Feng, W, Cheng, L, Liu, AA, Tsai, YC, Liu, LF & LaVoie, EJ 2008, 'Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)', Bioorganic and Medicinal Chemistry, vol. 16, no. 16, pp. 7824-7831. https://doi.org/10.1016/j.bmc.2008.06.046

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title = "Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)",

abstract = "Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.",

keywords = "Antitumor, Athymic mice, Cinnolines, Cytotoxicity, Human tumor xenografts, Isoquino[4,3-c]cinnolin-12-ones, Multidrug resistance, Topoisomerase",

author = "Mavurapu Satyanarayana and Wei Feng and Liang Cheng and Liu, {Angela A.} and Tsai, {Yuan Chin} and Liu, {Leroy F.} and LaVoie, {Edmond J.}",

year = "2008",

month = aug,

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doi = "10.1016/j.bmc.2008.06.046",

language = "English",

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AU - Satyanarayana, Mavurapu

AU - Feng, Wei

AU - Cheng, Liang

AU - Liu, Angela A.

AU - Tsai, Yuan Chin

AU - Liu, Leroy F.

AU - LaVoie, Edmond J.

PY - 2008/8/15

Y1 - 2008/8/15

N2 - Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.

AB - Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.

KW - Antitumor

KW - Athymic mice

KW - Cinnolines

KW - Cytotoxicity

KW - Human tumor xenografts

KW - Isoquino[4,3-c]cinnolin-12-ones

KW - Multidrug resistance

KW - Topoisomerase

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AN - SCOPUS:49149111130

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JO - Bioorganic and Medicinal Chemistry

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Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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